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Data from TCGA, GTEx, and single-cell RNA-seq supported expression profiling, functional clustering, Cox regression survival analysis, and immune infiltration evaluation. In AML, CHIR-99021 treatment of THP-1 cells suppressed proliferation, triggered apoptosis, and induced S-phase arrest with decreased c-Myc. Results identify GSK3β as a superior pan-cancer diagnostic biomarker and a key regulator in oncogenic programs, including independent risk stratification in cytogenetic-risk AML.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":40,"@type":76,"position":81},"https://docshare.wps.com/document/research-report/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/gsk3-as-a-potential-regulator-in-aml-a-pan-cancer-multi-omics-analysis/345051/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/gsk3-as-a-potential-regulator-in-aml-a-pan-cancer-multi-omics-analysis/345051.png","ImageObject",300,407,{"name":92,"@type":93},"Ivy","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-09-23","2026-09-22",true,{"@type":102,"interactionType":103,"userInteractionCount":8},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"Which datasets and methods were integrated to study GSK3 isoforms in cancers?","Question",{"text":112,"@type":113},"The study integrated multi-omics data from TCGA, GTEx, and single-cell RNA-seq. It applied functional clustering, Cox regression survival analysis, immune infiltration profiling, and in vitro validation using AML cell lines treated with CHIR-99021.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How do GSK3α and GSK3β differ across cancers, particularly in AML?",{"text":117,"@type":113},"GSK3α was upregulated in 19 solid tumors but suppressed in AML, while GSK3β was elevated in 23 cancers and in high-risk AML subtypes (FAB-M0/M1). The results support divergent dysregulation of the two isoforms across malignancies.",{"name":119,"@type":110,"acceptedAnswer":120},"What were the in vitro effects of CHIR-99021 on AML THP-1 cells?",{"text":121,"@type":113},"CHIR-99021 (10 μM) significantly suppressed THP-1 proliferation, induced apoptosis, and caused S-phase cell cycle arrest. It also led to downregulation of c-Myc.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},345051,1790193652,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":39,"category_name":40,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":8,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":139,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":145},549758252649,"https://ap-avatar.wpscdn.com/avatar/8000253669c5317157?_k=1778319167496531819","OPEN ACCESS  \nCitation: Qiu R, Zhou Y, Song S, Wang Z  \n(2026) GSK3β as a potential regulator in AML: A pan-cancer multi-omics analysis. PLoS One 21(3): e0344994. [https://doi.org/10.1371/](https://doi.org/10.1371/)[ ](https://doi.org/10.1371/)[journal.pone.0344994](journal.pone.0344994)  \nEditor: Zhanzhan Li, Xiangya Hospital Central South University, CHINA  \nReceived: September 29, 2025  \nAccepted: March 1, 2026  \nPublished: March 31, 2026  \nCopyright: © 2026 Qiu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.  \nData availability statement: The processed datasets generated and analyzed during the current study, including the normalized gene expression matrices, derived scores (e.g. , immune cell infiltration scores, survival data), and the original uncropped Western blot images(S1), are available in the Zenodo repository  \nRESEARCH ARTICLE  \nGSK3 β as a potential regulator in AML: A pan-cancer multi-omics analysis  \nRuyi Qiu1, Yingying Zhou2, Shuang Song3*, Zhejiong Wang1*  \n1 Department of Laboratory Medicine, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, Zhejiang Province, China, 2 Department of Laboratory Medicine, Huangyan Hospital of Wenzhou Medical University, Taizhou First People’s Hospital, Taizhou, Zhejiang Province, China, 3 Department of Pathology, Zhejiang Provincial Hospital of Traditional Chinese Medicine, Hangzhou, Zhejiang Province, China  \n* [1046463088@qq.com](1046463088@qq.com) (SS); [wangzhejiong@zcmu.edu.cn](wangzhejiong@zcmu.edu.cn) (ZW)  \nAbstract  \nThe distinct roles of GSK3 isoforms (GSK3α/β) in tumorigenesis and immune modulation remain poorly characterized across malignancies. We integrated multi-omics data from TCGA, GTEx, and single-cell RNA-seq to analyze GSK3α/β expression patterns in 31 cancers. Functional clustering, survival analysis (Cox regression), immune infiltration, and in vitro validation (AML cell lines treated with CHIR-99021) were performed. Integrated multi-omics analysis of 31 malignancies revealed divergent dysregulation of GSK3 isoforms: GSK3α was upregulated in 19 solid tumors but suppressed in AML, while GSK3β was elevated in 23 cancers and high-risk AML subtypes (FAB-M0/ M1, P = 0.0013) . GSK3β outperformed GSK3α as a pan-cancer diagnostic biomarker, achieving superior AUC in 9 tumors. Prognostically, high GSK3α predicted poor OS inACC (HR = 8.80, P = 0.0047) and MESO (HR = 2.75, P \u003C 0.0067), whereas GSK3β independently stratified cytogenetic-risk AML (HR = 4.22, P = 0.007) . Immune profiling uncovered isoform-specific TME modulation: GSK3α correlated with protumorigenic immune infiltration (Treg/Th17, r = 0.38), contrasting GSK3β’s broad negative associations with cytotoxic effectors (r = −0 .27) . Functional validation in AML THP-1 cells demonstrated that the GSK3 inhibitor CHIR-99021 (10 μM) significantly suppressed proliferation, induced apoptosis, and caused S-phase cell cycle arrest, concomitant with downregulation of c-Myc. These findings establish GSK3β as a key regulator of oncogenic programs inAML. This study provides a comprehensive pan-cancer atlas of GSK3 isoform-specific functionality, nominating GSK3β as a high-priority therapeutic target.  \nIntroduction  \nCancer persists as a leading global cause of mortality with profound socioeconomic burdens. Current therapeutic modalities face constraints: immune checkpoint inhibitors such as PD-1/PD-L1 blockers achieved durable responses in only 15–20% of solid tumors due to primary resistance and immune-related adverse events [ 1–3];  \nPLOS One | [https://doi.org/10.1371/journal.pone.0344994](https://doi.org/10.1371/journal.pone.0344994) March 31, 2026 1 / 17  \nvia the persistent identifier (doi: 10.5281/ zenodo.18058235) .  \nFunding: Funding su","cbCaisOF0IWidGlv","https://ap.wps.com/l/cbCaisOF0IWidGlv","pdf",2493484,17,"English","# Abstract\n# Introduction","[{\"question\":\"Which datasets and methods were integrated to study GSK3 isoforms in cancers?\",\"answer\":\"The study integrated multi-omics data from TCGA, GTEx, and single-cell RNA-seq. It applied functional clustering, Cox regression survival analysis, immune infiltration profiling, and in vitro validation using AML cell lines treated with CHIR-99021.\"},{\"question\":\"How do GSK3α and GSK3β differ across cancers, particularly in AML?\",\"answer\":\"GSK3α was upregulated in 19 solid tumors but suppressed in AML, while GSK3β was elevated in 23 cancers and in high-risk AML subtypes (FAB-M0/M1). The results support divergent dysregulation of the two isoforms across malignancies.\"},{\"question\":\"What were the in vitro effects of CHIR-99021 on AML THP-1 cells?\",\"answer\":\"CHIR-99021 (10 μM) significantly suppressed THP-1 proliferation, induced apoptosis, and caused S-phase cell cycle arrest. It also led to downregulation of c-Myc.\"}]","GSK3β as a potential regulator in AML - A pan-cancer multi-omics analysis | PDF",1790056368,43]